RT Journal Article
T1 Lack of Sterol Regulatory Element Binding Factor-1cImposes Glial Fatty Acid Utilization Leading to Peripheral Neuropathy
A1 Cermenati, Gaia
A1 Audano, Matteo
A1 Giatti, Silvia
A1 Carozzi, Valentina
A1 Porretta Serapiglia, Carla
A1 Pettinato, Emanuela
A1 Ferri, Cinzia
A1 D'Antonio, Maurizio
A1 De Fabiani, Emma
A1 Crestani, Maurizio
A1 Scuranti, Samuele
A1 Sáez, Enrique
A1 Azcoitia Elías, Iñigo
A1 Calavetti, Guido
A1 García Segura, Luis Miguel
A1 Melcangi, Roberto C.
A1 Caruso, Donatella
A1 Mitro, Nico
AB Myelin is a membrane characterized by high lipid content to facilitate impulse propagation. Changes in myelin fatty acid (FA) composition have been associated with peripheral neuropathy, but the specific role of peripheral nerve FA synthesis in myelin formation and function is poorly understood. We have found that mice lacking sterol regulatory element-binding factor-1c (Srebf1c) have blunted peripheral nerve FA synthesis that results in development of peripheral neuropathy. Srebf1c-null mice develop Remak bundle alterations and hypermyelination of small-caliber fibers that impair nerve function. Peripheral nerves lacking Srebf1c show decreased FA synthesis and glycolytic flux, but increased FA catabolism and mitochondrial function. These metabolic alterations are the result of local accumulation of two endogenous peroxisome proliferator-activated receptor-α (Pparα) ligands, 1-palmitoyl-2-oleyl-sn-glycerol-3-phosphatidylcholine and 1-stearoyl-2-oleyl-sn-glycerol-3-phosphatidylcholine. Treatment with a Pparα antagonist rescues the neuropathy of Srebf1c-null mice. These findings reveal the importance of peripheral nerve FA synthesis to sustain myelin structure and function.
PB Science Direct
SN 1550-4131
YR 2015
FD 2015-04-07
LK https://hdl.handle.net/20.500.14352/23231
UL https://hdl.handle.net/20.500.14352/23231
LA eng
NO Giovanni Armenise-Harvard Foundation
NO Fondazione CARIPLO
NO Italian Ministry of Health
DS Docta Complutense
RD 13 abr 2025